This study reports on the direct effect of the envelope glycoprotein (gp120) of the human immunodeficiency virus type 1 (HIV-1) on human monocyte function. Addition of preparations of purified gpl20 from the HIV-1 to human monocytes resulted in the production ofinterleukin 1 (IL-1) and arachidonic acid metabolites from the cyclooxygenase and lipoxygenase pathways. Quantification of prostaglandin E2 (PGE2) and IL-1 revealed an increase in both mediators with 50 ng of gpl20 per ml and an increase of 12-and 30-to 40-fold with 200-400 ng of gp120 per ml, respectively. Unlike native gpl20, the recombinant nonglycosylated gp120 fragments PB1-RF and PB1-IIIB, as well as one of the core structural proteins of HIV-1, p24, did not increase arachidonic acid metabolism or IL-1 activity. Cytofluorometric analysis revealed that gpl20 blocked the binding of OKT4A to the CD4 on monocytes, whereas OKT4 binding was unaffected. Involvement of the CD4 in signal transduction was further demonstrated by the ability of OKT4 and OKT4A monoclonal antibodies to increase monocyte PGE2, IL-1 activity, and nanogram amounts of IL-113.

Cell activation by phytohaemagglutinin, phorbol ester and by the supernatant of phytohaemagglutinin-stimulated peripheral blood mononuclear cells induces the expression and cytopathic effects of latent human immunodeficiency virus type-1 (HIV-1) in vitro. The lymphocyte surface protein CD4 has been identified as a receptor for HIV-1 and binds the viral envelope glycoprotein (gp120). In the light of evidence indicating that one natural function of CD4 is as a growth factor receptor, we examined the ability of native gp120 to activate resting CD4-bearing lymphocytes. Our results indicate that gp120 has innate biological activity as a result of a specific interaction with CD4, inducing increases in intracellular levels of inositol trisphosphate and of calcium, and in interleukin-2 receptor expression and cell motility.

ABSTRACT:The

The serological relationships among 32 isolates compose a single antigenic serotype.

The human immunodeficiency virus type 1 (HIV-1), the causative agent of acquired immunodeficiency syndrome, infects humans and chimpanzees. To determine the efficacy of immunization for preventing infection, chimpanzees were immunized with gp120 purified from human T-cell lymphotrophic virus type IIIB (HTLV-IIIB)-infected cell membranes and challenged with the homologous virus, HTLV-IIIB. A challenge stock of HTLV-IIIB was prepared by using unconcentrated HTLV-IIIB produced in H9 cells. The titer of the virus from this stock on human and chimpanzee peripheral blood mononuclear cells and in human lymphoid cell lines was determined; a cell culture infectivity of 104 was assigned. All chimpanzees inoculated intravenously with 40 cell culture infectious units or more became infected, as demonstrated by virus isolation and seroconversion. One of two chimpanzees inoculated with 4 cell culture infectious units became infected. Chimpanzees immunized with gp120 formulated in alum developed antibodies which precipitated gpl20 and neutralized HTLV-IIIB. Peripheral blood mononuclear cells from gp120-vaccinated and HIV-infected animals showed a significantly greater response in proliferation assays with HIV proteins than did peripheral blood mononuclear cells from nonvaccinated and non-HIV-infected chimpanzees. Two of the gpl20-alum-immunized chimpanzees were challenged with virus from the HTLV-IIIB stock. One animal received 400 cell culture infectious units, and one received 40 infectious units. Both animals became infected with HIV, indicating that the immune response elicited by immunization with gpl20 formulated in alum was not effective in preventing infection with HIV-1. Acquired immunodeficiency syndrome is an immunopathological manifestation which occurs following infection by human immunodeficiency virus (HIV). Vaccines have proven to be the most effective means of controlling viral

Repeated immunizations of goats, horses, or chimpanzees with envelope glycoprotein gpl20 isolated from human immunodeficiency virus type 1 (HIV-1) resulted in type-specific neutralizing-antibody responses, which began to decay approximately 20 days following the administration of antigen. This was true repeatedly for serum samples from animals hyperimmunized with gpl20s from either the HTLV-IIIB (IIIB) or the envelope-divergent HTLV-IIIRF (RF) HIV-1 isolates. Animals previously immunized with the IIIB gpl20 were then inoculated with purified RF gpl20. The first response in these animals was an anamnestic resurgence of neutralizing antibody to IIIB without detectable neutralizing antibody for RF. However, with later RF gpl20 boosts, the IIIB neutralizing-antibody titers fell and an RF type-specific neutralizing-antibody response developed. When assessed with other HIV-1 variants, no group-specific neutralizing antibody was seen in any of the vaccination protocols evaluated. These results will pose real obstacles in the development of an effective vaccine for HIV.

Multilocus isoenzyme electrophoresis was used to screen 47 field isolates of Yersinia ruckeri for electrophoretic variation at 15 enzyme loci. Only four electrophoretic types were observed, thus indicating that the genetic structure of Y. ruckeri is clonal. Forty-two isolates were of one electrophoretic type, a reflection of the low amount of genetic diversity extant in this species. Although sorbitol fermentation has been considered to be indicative of a second biotype, no significant gene frequency differences were found between the group of 20 isolates that readily used sorbitol as the sole carbon source and the group of 27 that did not.

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